Zilin Wang

Carbon quantum dots (CQDs) have emerged as promising nanomaterials for biomedical applications, including bioimaging, drug delivery, biosensing, and tissue regeneration, owing to their favorable biocompatibility, tunable physicochemical properties, and diverse biological activities. Despite accumulating evidence of their regenerative potential, the mechanisms by which CQDs regulate complex tissue regeneration remain insufficiently integrated. In this Review, we synthesize recent advances in the biomedical applications of CQDs, with particular emphasis on material selection for specific disease contexts and their direct and indirect regulatory roles in tissue regeneration. We examine how CQDs modulate cellular functions, angiogenesis, stem cell differentiation, the immune microenvironment, and redox homeostasis through molecular pathways, and how their physicochemical properties shape these biological effects and regenerative outcomes. We further discuss emerging strategies for functional optimization, including multifunctional and stimuli‐responsive CQD systems. Finally, we critically assess key translational barriers, including structural characterization, biological evaluation, safety assessment, material standardization, and manufacturing consistency. By linking CQDs’ properties to molecular mechanisms and regenerative outcomes, this Review provides a conceptual framework for the rational design of CQDs and the development of more effective regenerative therapies.

BACKGROUND Large language model-based intelligent standardized patient systems offer a scalable solution for clinical skills training, yet rigorous comparisons against active pedagogical controls remain scarce, and the mechanisms underlying their effectiveness are poorly specified. This study evaluated an LLM-based intelligent SP system compared with small-group, tutor-facilitated case discussion in dental education, with the explicit objective of disentangling the role of differential individual active learning time as a potential mediator of observed effects. OBJECTIVE To evaluate an LLM-based intelligent standardized patient system compared with small-group, tutor-facilitated case discussion in dental education, and to disentangle the role of differential individual active learning time as a potential mediator of observed effects. METHODS In this single-center, parallel, open-label randomized trial conducted from May to June 2025, 60 third- and fourth-year dental students were randomized 1:1 to the AI-SP group (n=30) or the TC-SG group (n=30). The AI-SP group completed six interactive virtual patient modules powered by DeepSeek-V3 with automated feedback, while the TC-SG group discussed identical cases in groups of four to five students with a tutor. The primary outcome was the adjusted post-intervention mini-CEX Overall Score assessed by a blinded expert panel using ANCOVA with baseline adjustment. Secondary outcomes included AI-generated communication metrics and clinical self-efficacy. The study design inherently produced substantially different individual active learning time between arms—approximately 110–120 minutes per session for AI-SP versus 24–30 minutes for TC-SG—which we explicitly treated as a design-defined dose parameter. Due to significant baseline imbalances in secondary AI-generated metrics favouring the TC-SG group, causal inferences were restricted to the primary outcome, where baseline balance was confirmed. RESULTS Fifty-nine participants completed the trial (AI-SP=30, TC-SG=29). For the primary outcome, the AI-SP group showed significantly higher adjusted post-intervention mini-CEX Overall Score compared with TC-SG (adjusted mean difference [aMD]=0.68; 95% CI, 0.29–1.07; P=0.001; η²p=0.22). This effect size corresponded to the substantial difference in individual practice density between the two conditions. For AI-generated secondary metrics, despite significant within-group improvements in the AI-SP group (all P<0.001), no significant between-group differences were observed at post-intervention for Accuracy (P=0.059) or Interactivity (P=0.161), indicating comparable endpoint performance. Given the baseline imbalance in these metrics, we interpret these null between-group differences conservatively, without claims of catch-up or superiority. An exploratory regression analysis treating estimated individual active learning time as a continuous predictor revealed a significant association with mini-CEX improvement (β=0.34, P=0.002), supporting the dose-response interpretation. CONCLUSIONS The AI-SP system, by affording substantially higher individual active learning density, produced superior expert-assessed clinical outcomes compared with small-group discussion. However, this advantage is confounded by unequal practice time and cannot be attributed solely to AI intelligence. Our findings suggest that AI-SP functions primarily as an effective pedagogical platform for scaling individual deliberate practice opportunities. Future research must employ dose-equated designs to isolate the unique contribution of AI-generated feedback from the general benefits of increased active learning time.

Background: Medication‐related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive or antiangiogenic therapy, yet its molecular mechanisms remain poorly understood. This study aimed to identify potential core genes involved in MRONJ pathogenesis through integrative bioinformatics analysis. Methods: GSE7116 dataset (PBMC samples from 11 MRONJ and 10 non‐MRONJ multiple myeloma patients on bisphosphonates) was analyzed. DEGs were identified using GEO2R. Functional enrichment, PPI network, hub gene identification, ROC‐based diagnostic evaluation, and independent qRT‐PCR validation were performed. Results: 241 DEGs (212 down, 29 up) were identified, enriched in immune/inflammatory responses and NOD‐like receptor/NF‐κB pathways. Ten hub genes ( TNF , ACTB , IL1B , JUN , CXCL8 , CXCR4 , PTPRC , IL1A , HSP90AB1 , RHOA ) were identified. Four of them ( HSP90AB1 , RHOA , CXCL8 , IL1B ) showed high diagnostic accuracy (AUC 0.864–0.936) and were validated by qRT‐PCR. Conclusion: This integrative bioinformatics analysis, combined with ROC evaluation and experimental qPCR validation, identifies immune‐ and inflammation‐related hub genes as central to MRONJ pathogenesis. A four‐gene signature ( HSP90AB1 , RHOA , CXCL8 , IL1B ) shows high diagnostic accuracy (AUC 0.864–0.936) and is proposed as a peripheral blood‐based diagnostic panel. The widespread downregulation of inflammatory genes in PBMCs suggests systemic immunosuppression rather than overt inflammation, offering new insights for immunomodulatory strategies.

Oral and maxillofacial bone defects present significant clinical challenges. This study developed a 3D-printed terbium-doped carbonate hydroxyapatite scaffold to enhance bone regeneration. The Tb-CHA scaffold was fabricated via 3D printing and evaluated for its physicochemical properties, biocompatibility, biodegradability, and mechanical strength. In vitro experiments assessed the scaffold's effects on proliferation and differentiation of pre-osteoblasts (MC3T3-E1 cells), while in vivo osteogenic and angiogenic capabilities were tested using a rat calvarial defect model. The Tb-CHA scaffold exhibited suitable mechanical properties, biodegradability, and biocompatibility, providing an optimal microenvironment for bone regeneration. In vitro, Tb-CHA significantly enhanced MC3T3-E1 cell proliferation and osteogenic differentiation. In vivo, the scaffold promoted robust bone tissue and vasculature regeneration in rat calvarial defects, outperforming conventional materials. Tb-CHA represents a promising biomaterial for bone defect repair, combining the advantages of 3D printing precision and the osteogenic potential of terbium. This study pioneers the application of rare earth elements in bone tissue engineering, offering a novel strategy for clinical challenges in dentistry and orthopedics.

To systematically evaluate the capability of three large language models (LLMs)—GPT-4o, Grok-3, and DeepSeek—in interpreting and translating cl

Objective: This study aimed to systematically analyze the clinical characteristics, diagnostic controversies, and treatment outcomes of branchiogenic carcinoma (BC) to validate its status as a distinct pathological entity and evaluate the role of molecular biology in distinguishing primary carcinoma from metastatic lesions, thereby optimizing evidence‐based diagnostic and therapeutic strategies. Methods: A retrospective cohort study was conducted, screening PubMed databases (1919–2025) for BC cases adhering to Martin‐Huber, Wolff, and Khafif diagnostic criteria. Inclusion criteria: (1) Tumor location: Anatomically confined to branchial cysts/sinuses. (2) Pathology: Histopathological evidence of gradual transition from normal squamous epithelium to invasive carcinoma. (3) Primary exclusion: No detectable primary malignancy after comprehensive evaluation. (4) Occult tumor assessment: No occult primaries identified during follow‐up. Exclusion criteria: (1) Nonprimary BC (e.g., metastatic SCC). (2) Ambiguous diagnoses (nonconforming histology or criteria). Thirty‐three cases met inclusion criteria (33 for treatment analysis; 30 with full follow‐up). Demographic, clinicopathological, and treatment data were collected. Survival rates and risk factors were analyzed using Kaplan–Meier methods and Cox regression models. Results: BC predominantly affected males (2.2:1 male‐to‐female ratio), with a peak incidence at 50–60 years. Squamous cell carcinoma (SCC) accounted for 85.7% of cases, and 80.0% originated in the second branchial cleft. Integration of molecular imaging (18F‐FDG PET/CT) with traditional diagnostic criteria significantly reduced occult primary tumor misdiagnosis. Disease‐free survival (DFS) reached 86.7% with surgery alone, yet an 11.4% recurrence rate underscored the need for adjuvant therapy. HPV positivity (5.7%) correlated significantly with prognosis. Conclusion: While BC's status as an independent entity requires further molecular validation (e.g., whole‐exome sequencing), this study highlights the necessity for international multicenter collaborations to build large‐scale databases and explore chronic inflammation and immune microenvironment roles in carcinogenesis, advancing precision oncology paradigms.

Multidrug resistance in Gram-negative bacteria has become a significant global public health challenge, threatening human health and clinical treatment outcomes. The unique outer membrane structure of these pathogens greatly limits antibiotic penetration, serving as the core mechanism of resistance. This paper systematically analyses antimicrobial strategies targeting the outer membrane of Gram-negative bacteria, mainly including: (1) directly disrupting the outer membrane structure and enhancing drug permeability; (2) inhibiting the biosynthesis or transport pathways of key outer membrane components; (3) using natural pathways to facilitate drug entry into the cell; (4) inhibiting efflux pumps to block efflux functions; (5) optimizing the physicochemical properties of drugs to enhance outer membrane permeability and using nanotechnology to develop new drug delivery systems. In recent years, BAM complex inhibitors like darobactin and xenorceptides have efficiently blocked the assembly of outer membrane proteins through a novel mechanism and exhibited excellent broad-spectrum antibacterial activity. Iron carrier-conjugated drugs like cefiderocol have also successfully transitioned to clinical use, showing significant efficacy in treating infections caused by various multidrug-resistant bacteria. Despite promising strategies targeting the outer membrane, drug development faces challenges, such as poor selectivity, potential toxicity, and evolving resistance mechanisms. Future research must delve deeper into the biosynthesis and regulatory mechanisms of the outer membrane, aiming to develop more selective and safer innovative antimicrobial drugs and delivery systems to effectively combat the growing threat of multidrug-resistant Gram-negative bacterial infections.

Medication‐related osteonecrosis of the jaw (MRONJ) is a severe oral disease induced by anti‐resorptive and anti‐angiogenic drugs. It is characterized by jawbone necrosis, infection, and impaired bone healing, severely affecting the patient's quality of life. Although the pathogenesis of MRONJ has been extensively studied, the exact pathophysiological process remains unclear. The currently accepted mechanisms include inhibition of bone formation, inhibition of angiogenesis, and oral microbial infection, which interact to form a vicious cycle, further exacerbating disease progression. This review explores the effects of anti‐resorptive and anti‐angiogenic drugs on MRONJ, the role of microbial infection in disease development, current non‐surgical and surgical treatment strategies, and future research directions, aiming to provide references for clinical diagnosis and treatment as well as research.

Efferocytosis is a crucial process by which apoptotic cells are removed by phagocytes such as macrophages. It not only maintains tissue homeostasis and immune tolerance, but also plays a central role in tissue repair and disease regulation. In recent years, dysfunction of efferocytosis has been found to be closely related to various diseases, such as atherosclerosis, cancer, and chronic inflammatory conditions. Activating or remodeling efferocytosis has become a key direction in regenerative medicine and precision therapy. This review systematically summarizes the molecular mechanisms and immunomodulatory functions of efferocytosis, highlights its roles in various models of tissue injury and repair, and explores recent advances in targeted modulation of efferocytosis using nanomaterials, biomaterial scaffolds, and hydrogels. By focusing on the biological logic of “life from death,” this article aims to provide a theoretical foundation and strategic support for the translational applications of efferocytosis in tissue engineering, immunotherapy, and disease intervention. Furthermore, it highlights the synergistic potential of combining nanomaterials, hydrogels, and biological scaffolds to create next-generation efferocytosis-driven therapies, thereby offering a multidisciplinary perspective on overcoming current challenges in clinical translation. Specifically, this synergistic strategy holds particular promise in addressing key clinical challenges such as overcoming tumor immunosuppression and promoting vascularization in chronic wounds, providing a targeted approach to enhance therapeutic outcomes in these complex pathological contexts.